Acquired immunity to pyelonephritis must operate under chemical conditions encountered in no other body fluids. We have demonstrated that such immunity can be produced by vaccination in retrograde pyelonephritis, but its mechanism is obscure and it functions in an unusual milieu against E. coli and other organisms that are harmless elsewhere. A study will be made, therefore, of the complex interactions among antibody, inflammatory cells, and the hypertonic solutes peculiar to the renal medulla. The information obtained will be used to imporove the antibody response during vaccination and infection, and to determine the role of lymphocytes and macrophages in eliminating infection and damaging the kidney. The ultimate objectives are to prevent kidney infection by active or passive immunization and to reduce damage in pyelonephritis by modifying and improving the immune response.